The Penn Diabetes Research Center (DRC) participates in the nationwide interdisciplinary program established over four decades ago by the NIDDK to foster research in diabetes and related metabolic disorders. The mission of the Penn DRC is to support and develop successful approaches to the prevention, treatment, and cure of diabetes mellitus. Administered by the University of Pennsylvania, the Penn DRC currently serves 127 diabetes-oriented investigators, primarily from the Perelman School of Medicine at the University of Pennsylvania School but also from other Schools within the University as well as collaborating local institutions including Thomas Jefferson University, Temple University School of Medicine, the Monell Chemical Senses Institute, the Wistar Institute, and Rutgers University. Overall direct costs of $67M support the work of these investigators. The Penn DRC is highly interactive and interdisciplinary, representing many basic science and clinical departments. The Research Base of the Penn DRC is organized in 4 focus groups: 1) Type 1 Diabetes, with a focus on beta cell biology and Pathology; 2) Type 2 Diabetes, focused on signaling by insulin and other hormones; 3) Obesity; and 4) Cardiovascular Metabolism and Complications. The Penn DRC facilitates and supports diabetes research in a variety of ways. Six Biomedical Research Cores facilitate the work of Penn DRC investigators: Functional Genomics Core; Islet Cell Biology Core, Mouse Phenotyping, Physiology, and Metabolism Core; Radioimmunoassay/Biomarkers Core; Transgenic and Chimeric Mouse Core, and Viral Vector Core. Collaborative research and application of emerging technologies to diabetes investigation are further promoted by the Regional Metabolomic Core at Princeton. A Pilot and Feasibility Grant Program that has been highly successful over decades serves to nurture new investigators and to foster new initiatives in diabetes research. A broad and intensive Enrichment Program organizes weekly Diabetes and Endocrinology Research seminars, special events, and an annual Spring Diabetes Symposium, all designed to enhance communication and collaboration of Penn DRC investigators while keeping them abreast of the latest discoveries. Penn DRC investigators mentor trainees at every level (undergraduate, predoctoral, and post-doctoral Ph.D., M.D., and combined M.D./Ph.D.), and the Enrichment Program provides a superb environment for training in diabetes research. The Biomedical Cores, Pilot and Feasibility Grant Program, and Enrichment Program are coordinated and publicized by an Administrative Component that governs the DRC. Its organizational structure, including the Director and Associate Director, Executive Committee, Committee of Core Directors, and external as well as internal advisory boards, functions to maintain the diabetes-related research at the Penn DRC at the forefront of biomedical science.